Detection of Somatostatin Receptors, SSTR2A and SSTR5, in TSH Producing Pituitary Adenomas: Patho-Clinical Correlation
M Takei, H Kajiya, C Inomoto, S Takekoshi, A Teramoto, RY Osamura. Tokai University School of Medicine, Kanagawa, Japan; Nippon Medical School, Tokyo, Japan
Background: Somatostatin analogue (octreotide) targets SSTR subtypes 2 and 5. In order to predict the response of the SSTR targeted therapy by somatostatin analogue (octreotide) in the pituitary adenomas, immunohistochemical detection of SSTRs is essential for appropriate treatment. Even though TSHomas are rare, they usually are associated with Graves' disease and macroadenomas which sometimes require octreotide for the residual tumors. Therefore, in particular, this study is aimed at to elucidate the expression of SSTRs in TSHomas with the special reference to the pre-operative response to octreotide.
Design: The pituitary adenomas from total 14 cases of TSHomas (female:12 cases,male:2 cases) were subjected to the following study. Nine cases were macroadenomas and five cases were microadenomas. Preoperative serum TSH levels were 0.464-9.802U/ml (average 6.28). The formalin-fixed paraffin embedded (FFPE) sections were immunohistochemically stained for SSTR2A and SSTR5 (the antibodies supplied from Gramsch Laboratories, Germany) by ABC method after appropriate antigen retrieval with autoclave. The staining results were classified into 1+ (<25%), 2+ (<75%), 3+ (>75%) by the ratio of positive cells. Response of serum TSH by preoperative somatostatin analogue suppression test was also measured. In three cases, real time RT-PCR was performed for SSTR2 and SSTR5.
Results: Immunohistochemically, all cases were positive for SSTR2A. The staining was interpreted as positive if it is localized on the cell membrane. Incidence of the positive staining for SSTR2A was as follows;1+ (14.2%), 2+ (35.7%), 3+ (50.0%). SSTR5 was positive in eight cases (57.1%). Incidence of the positive staining for SSTR5 was as follows; cell membrane (35.7%), cytoplasm (21.4%). In real time RT-PCR analysis, SSTR2mRNA was overexpressed in 2 cases. When these staining were compared with pre-operative suppression test, the cases with low serum TSH suppression were correlated with weak (1+) immunohistochemical staining for SSTR2A. Good response to preoperative octreotide was well correlated with 3+ immunohistochemical staining for SSTR2A.
Conclusions: Our studies showed that TSHomas expressed SSTR2A and SSTR5 by immunohistochemistry which predict the response to the somatostatin analogue (octreotide). It is suggested that the cases with high (3+) SSTR2A, being as a better target molecule, expect better response to the octreotide.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 94, Tuesday Afternoon